The incidence of advanced liver disease in the aging population is increasing and often these patients are not candidates for liver transplant. We explore the age-related modulation of hepatocyte stress signals, myofibroblast transdifferentiation and innate immune responses in the aging liver. We discovered that the phagocytic NADPH oxidase 2 can be activated by an interaction with the adaptor p52Shc, creating oxidative burst in hepatocytes generating accelerated fibrogenic responses, and worsening insulin sensitivity (Hepatology, 2020). We are now pursuing translational projects to evaluate whether Shc could be targeted as a novel therapy for NASH.
